Now, a team of researchers at the National Institute of Allergy and Infectious Diseases (NIAID) are beginning to set up the first human trial for an HIV vaccine that induced an exciting level of immune response when tested in mice, guinea pigs, and monkeys.

According to their paper, published in Nature Medicine, the vaccine targets a protein on the surface of the HIV particle that is essential to the mechanical process the virus uses to slip inside a host’s cells. The HIV-1 fusion peptide, as it is known, was first identified as a possible vaccine target in 2016, when they were analyzing the HIV-crippling antibodies that a patient who had been living with HIV for several years was naturally producing.

This work revealed that the individual’s immune system was creating a line of particularly effective “broadly neutralizing antibodies” whose epitope – its binding site on the virus – was the end tip of the HIV-1 fusion peptide. Upon closer examination, the team, led by John Mascola and Peter Kwong, was thrilled to see that the epitope bears all the key features necessary for constructing an effective vaccine around: it remains consistent across multiple strains of the rapidly evolving virus and it is not obscured from immune cells by many added sugar molecules like some viral surface proteins.

Next, Kwong and Mascola’s lab set out to engineer a protein that would prompt a recipient’s immune system to create large numbers of broadly neutralizing antibodies specific to the HIV-1 fusion peptide epitope. In the current study, they developed and tested various formulations of an eight amino acid-long protein that is bonded to an immune reaction-boosting carrier molecule, combined with duplicates of the larger cell-entry surface protein subunit that the HIV-1 fusion peptide is part of.

This protein structure diagram illustrates the location of the fusion peptide epitope (red) on the HIV spike (green), which projects out of the viral membrane (grey). The diagram also shows how a broadly neutralizing antibody (yellow) binds to the fusion peptide. NIAID

When the best of these vaccine candidates were given to mice, the animals' immune systems produced antibodies that successfully attached to the fusion protein and neutralized 31 percent of viruses from a panel of 208 HIV strains collected from regions around the world.

Subsequent experiments in guinea pigs and rhesus monkeys proved that the vaccine works in multiple species – an encouraging sign that it will also work in us.

"NIH scientists have used their detailed knowledge of the structure of HIV to find an unusual site of vulnerability on the virus and design a novel and potentially powerful vaccine," NIAID Director Dr Anthony S. Fauci said in a statement. "This elegant study is a potentially important step forward in the ongoing quest to develop a safe and effective HIV vaccine."

According to their press release, the NIAID group are currently tweaking the vaccine using data from monkey trials in order to have the most ideal version ready for the upcoming phase 1 assessment in human subjects.